In this study, hollow fiber membrane extraction combined with ambient ionization mass spectrometry ( AMS) was developed for the simultaneous determination of 7 perfluorinated compounds ( PFCs) in aqueous solution, including perfluoroheptanoic acid ( PFHpA ) , perfluorooctanoic acid ( PFOA ) , perfluorooctane sulfonate acid ( PFOS ) , perfluorononanoic acid ( PFNA ) , perfluorodecanoic acid ( PFDA ) , perfluoroundecanoic acid ( PFUdA) , and perfluorododecanoic acid ( PFDoA) . PFCs were detected in negative ion mode using selective reaction monitoring ( SRM) mode. The extraction time and the pH value of extraction solution were optimized. 13 C4-PFOS and 13 C4-PFOA were used as internal standards for quantitative analysis. The method showed good linearity with correlation coefficient values ( r2 ) greater than 0. 991 for the seven target PFCs. With the exception of PFHpA, the limit of detection ( LOD) for other six PFCs was within ranges from 0. 8 to 2. 7 ng/L while the limit of quantitative (LOQ) was from 2. 7 ng/L to 8. 9 ng/L. The enrichment factor of five PFCs was more than two hundred. The developed method was applied to detect the seven PFCs in tap water and Pearl River water, and they were all not detected. The recoveries were within the ranges of 88. 5%-108. 3% and 94. 2%-116. 7% when 40 ng/L and 400 ng/L PFCs were spiked into tap water, respectively. In terms of the Pearl River water, the recoveries were within the ranges of 75. 0%-102. 6% and 81. 2%-97. 6% when 40 ng/L and 400 ng/L PFCs were spiked, respectively.

Objective To analyze the blood flow velocities in middle cerebral artery with Rasmussen encephalitis. Methods8 patients with Rasmussen encephalitis were detected bilateral middle cerebral artery in both period of onset and intermission during simple partial seizures with Transcranial Doppler. ResultsThe mean velocity variance between focus side and non-focus side was minimums among the 3 indexes observed. The mean velocity of MCA displayed uneven increase during seizures. ConclusionThe mean velocity was the most stable index for judging.

Objective: To study the effects of altitude exposure and altitude exposure on mental health of Tibetan cadres. Methods: 105 cadres in Tibet were selected as the research objects. Among them, 74 cadres in Shannan and Lhasa of Tibet (average altitude 3 680 m), 31 in Shigaze and Ali (above 3 800 m) and 14 in Ali (above 4 300 m) were selected. Using Symptom Checklist 90 (SCL-90), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and Ascension Insomnia Scale (AIS), 105 Tibetan aid cadres were tested by SAS, SDS, AIS and SCL-90 one week after entering Tibet and one week before leaving the plateau. The scores were collected and the mental health and sleep status of Tibetan aid workers were measured. Results: The number of positive items of SCL-90 of 105 Tibetan cadres increased from (13.21±9.05) one week after entering Tibet to (38.35±18.84) one week before leaving Tibet. SAS, SDS and AIS also increased from (25.49±5.19), (26.41±5.15), (5.16±3.54) points one week after entering Tibet to (36.78±7.53), (41.42±9.15), (8.71±4.64) points one week before leaving Tibet. The difference was significant in the last week (Z = 8.420, 8.689, 6.277, P<0.01). The correlation analysis between SCL-90 and SAS, SDS and AIS showed that SCL-90 was positively correlated with SAS, SDS and AIS scores (r = 0.651, 0.616, 0.356, P<0.01). Different altitudes have an effect on the mental health of Tibetan aid cadres. The paranoid item scores of Tibetan aid cadres with altitude>4 300 m in SCL-90 were (1.68 ± 0.50) points, which were higher than those of Tibetan aid cadres with altitude<4 300 m (1.24±0.28) points and (1.40± 0.38) points. The difference was statistically significant (F=5.255, P=0.007); The SDS scores of Tibetan aid cadres with altitude>4 300 m were (46.64 ± 7.24) points, which were higher than those of Tibetan aid cadres with altitude<4 300 m (40.76 ± 8.99) points and (40.58 ± 8.28) points. The difference was statistically significant (F=3.223, P=0.044). Conclusion Exposure to high altitude affects the mental health of cadres assisting Tibet to varying degrees. The mental health of cadres assisting Tibet deserves attention.

Objective To analyze the iodine nutritional status of children and pregnant women in Liaoning Province,and the iodine content of edible salt suitable for iodine nutrition level,to provide a basis for adjusting the suitable salt iodine content standard of key population.Methods In 2015-2018,a cross-sectional survey method was used to conduct iodine nutritional status surveys in counties (districts) within the jurisdiction of Liaoning Province.One township (community) was selected in each county (district)according to the east,west,south,north,and middle directions.Forty children aged 8-10 (age and gender distribution balanced) and 20 pregnant women were selected in each township (community),urine and household salt samples were collected from children and pregnant women,to test urine and salt iodine levels;and the water samples from all township (community) water supply plants in the province were collected for water iodine detection in 2017;and all respondents were calculated the dietary iodine intake.The multi-order linear curve was used to fit the salt iodine content suitable for children and pregnant women.Results A total of 1 549 townships (communities) were surveyed,including 1 125 centralized water supply townships (communities) with water iodine ＜ 40 μg/L;50 820 children aged 8-10 and 26 707 pregnant women were selected from the centralized water supply towns.The average iodine content of edible salt was 24.0 and 23.9 mg/kg,respectively.The median urinary iodine level of children was 168.5 μg/L,at the appropriate level of iodine;the median urinary iodine level of pregnant women was 137.8 μg/L,at the deficiency level of iodine.The average dietary intake of iodine in children was 228.4 μg/d,which was 3.51 times of the standard iodine requirement (EAR,65 μg/d) and 2.54 times of the recommended intake (RNI,90 μ g/d).The average dietary intake of iodine in pregnant women was 273.4 μg/d,which was 1.71 times of the EAR (160 μg/d) and 1.19 times of the RNI (230 μg/d),and 21.4％ (5 728/26 707) of pregnant women had lower iodine intake than RNI,the iodine intake was insufficient.After multi-level linear curve fitting combined with monitoring data,the iodine content range of edible salt in children's urine was suitable and the iodine intake in RNI-tolerable intake (UL,300 μg/d) was 13-25 mg/kg (20 mg/kg + 20％);the iodine content range of edible salt in pregnant women's urinary iodine was suitable and the iodine intake in RNI-UL (600 μg/d) is 25-37 mg/kg (31 mg/kg + 20％).Conclusions Under the current salt iodine content standard (25 mg/kg) in Liaoning Province,children's iodine nutrition is generally at the level of iodine appropriate;pregnant women's iodine nutrition is generally at the level of iodine deficiency.It is recommended that all regions should revise the iodine content standard for edible salt in due course in combination with the iodine nutritional status of key populations within the jurisdiction.

Objective: To elucidate the association between large conductance calcium-activated potassium channels (BK_Ca) in the paraventricular hypothalamic nucleus (PVN) and sympathetic outflow in rats with chronic heart failure (CHF) . Methods: Male Wistar rats (6-7 weeks old) were randomized to sham operated group and CHF group (coronary artery ligation) . Two weeks after operation, BK_Ca inhibitor Iberiotoxin (IBTX) was infused into PVN by osmotic minipumps, rats were divided into following groups: sham+aCSF, CHF+aCSF, sham+low dose IBTX (0.125 nmol/nl) , CHF+low dose IBTX, sham+moderate dose IBTX (1.25 nmol/nl) , CHF+moderate dose IBTX, sham+ high dose IBTX (12.5 nmol/nl) , and CHF+high dose IBTX (n=6 each) . Additional rats were grouped as follows: sham+vehicle, sham+KCNMB4 knockdown (by rAAV2-KCNMB4 shRNA virus injection in PVN) , CHF+vehicle, CHF+ KCNMB4 knockdown group (n=6 each) . The cardiac function was determined by echocardiography, left ventricular hemodynamics were measured invasively, renal sympathetic nerve activity (RSNA) was recorded at 6 weeks after coronary artery ligation or sham operation. The contents of norepinephrine (NE) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in plasma were determined by enzyme-linked immunosorbent assay. The protein and mRNA expression of KCNMB4 in PVN were measured by immunofluorescence staining, Western blot, and real-time PCR, mRNA expression of BK_Ca in PVN was detected by real-time PCR. Results: Compared with the sham operation group, the cardiac function of the heart failure group was significantly reduced (P<0.05) , and the plasma NE and the serum NT-proBNP were significantly elevated (P<0.05) . The protein and mRNA expression of KCNMB4 in PVN were obviously down-regulated in CHF rats (P<0.05) . After perfusion of IBTX or KCNMB4 knockdown by microinjection of rAAV2-KCNMB4 shRNA virus,right ventricular weight/body weight and lung weight/body weight ratio as well as left ventricular end-diastolic diameter were increased and left ventricular ejection fraction was decreased (all P<0.05) , the sympathetic driving indexes was increased in sham rats, changes of these parameters further aggravated in CHF rats (P<0.05) . KCNMB4 knockdown further downregulated protein expression in PVN of CHF rats. Conclusion Downregulation and blunted function of BK_Ca in PVN may contribute to sympathoexcitation and deterioration of cardiac function in rats with chronic heart failure.

BACKGROUND:Lower limb peri-knee muscle strength training and neuromuscular electrical stimulation are generally safe and effective rehabilitation methods for patellofemoral joint pain,but the mechanism of their intervention is still unclear. OBJECTIVE:To determine the effect of muscle strength training combined with neuromuscular electrical stimulation on pain,lower extremity function and biomechanical characteristics in patients with patellofemoral pain. METHODS:Thirty-seven patients with patellofemoral pain were randomly divided into muscle strength training combined with electrical stimulation group(trial group,n=19)and muscle strength training group(control group,n=18).Both groups underwent intervention training for 6 weeks,three times a week.The visual analog scale and anterior knee pain scale were used to evaluate the pain level and functional level of the knee.Kinematic and kinetics data during running were collected by using an infrared motion capture system and a three-dimensional force platform simultaneously.A two-way analysis of variance with repeated measures(group*time)was applied to analyze the data. RESULTS AND CONCLUSION:(1)After the intervention,the visual analog scale scores of the trial group and the control group were significantly decreased(P<0.001),and the anterior knee pain scale scores were significantly increased(Ptrial group<0.001,Pcontrol group=0.001)in the trial group and control group.The anterior knee pain scale scores of the trial group were significantly higher compared to the control group after the intervention(P=0.001).(2)The peak knee flexion angle(P=0.011),peak knee extension moment(P<0.001),the peak knee internal rotation moment(P=0.008),the peak patellofemoral stress(P<0.001)and the peak patellofemoral contact force(P<0.001)were significantly decreased in the trial and control groups during running after the intervention compared with those before the intervention.(3)In conclusion,both muscle strength training and muscle strength training combined with electrical stimulation training are helpful to improve the subjective pain and lower limb function of patellofemoral pain patients,enhance the movement pattern during running and reduce the stress of the patellofemoral joint.Compared with muscle strength training alone,muscle strength training combined with electrical stimulation can improve lower limb function more significantly.

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO_2-x ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO_2-x to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90α (HSP90α), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO_2-x demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.